Cytokine Expression Pattern and Protein-Protein interaction network analysis of Leucocyte Rich Platelet Rich Fibrin and

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ORIGINAL ARTICLE

Cytokine Expression Pattern and Protein-Protein interaction network analysis of Leucocyte Rich Platelet Rich Fibrin and Injectable Form of Platelet Rich Fibrin Sharmila Jasmine 1 & Annamalai Thangavelu 1 & Rajapandiyan Krishnamoorthy 2 & Mohammed A. Alshuniaber 2 & Ali A. Alshatwi 2 Received: 15 April 2020 / Accepted: 24 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Purpose Platelet-rich fibrin (PRF) such as leucocyte-rich PRF (L-PRF) and injectable form of PRF (i-PRF) are widely used in various surgical applications. L-PRF- and i-PRF-derived cytokine variations and functional pathways are still unexplored. The aim of the study was to evaluate the expression pattern of Th1-, Th2-, and Th17-related cytokines by L-PRF and i-PRF under in vitro. Methods Cytokine levels were evaluated using multi-analyte ELISArray kit. Using elevated level of cytokines, the proteinprotein interaction and pathway were predicted by computational method. Results The expressed cytokine levels were higher in L-PRF than in i-PRF. Specifically in L-PRF, IL8, IL2, IL6, and IL1A were expressed abundantly, whereas IL4, IL10, and IL6 were significantly high in i-PRF. Furthermore, protein-protein interaction (PPI) networks (cytokine-cytokine interactions) and pathway analyses were predicted using higher-order cytokines. PPI networks and gene ontology enrichment analysis showed functional variations between L-PRF and i-PRF. Kyoto Encyclopedia of Gene and Genome pathway analysis found that L-PRF mediates NF-k B signaling, Toll-like receptor signaling (TLR), and MAPK signaling via T-cell receptor signaling pathway. i-PRF is significantly involved in JAK-STAT signaling pathway through upregulation of STAT1. Conclusion Our study concludes that L-PRF and i-PRF act via different pathways that confirm functional variations between them. Therefore, we speculate that L-PRF may be effective in acute phase of chronic wounds such as in diabetes mellitus and immunocompromised patients whereas i-PRF may have a better outcome in acute wounds. Keywords Platelet-rich fibrin . Proinflammatory cytokine . Anti-inflammatory cytokine . Acute wound . Chronic wound

Introduction Wound healing after surgical intervention is a complex process that involves several overlapping phases such as inflammation, granulation tissue formation, re-epithelization, matrix formation, and remodeling. The clotting * Sharmila Jasmine [email protected] 1

Department of Oral Maxillofacial Surgery, Rajah Muthiah Dental College and Hospital, Annamalai University, Chidambaram, Tamil Nadu 608002, India

2

Nanobiotechnology and Molecular Biology Research Lab, Department of Food Science and Nutrition, College of Food Science, King Saud University, Riyadh 11541, Kingdom of Saudi Arabia

cascade is initiated at the wound site and results in hemostasis [1]. Interaction among cytokines, growth factors, chemokines, and chemical mediators regulates these events through complex integration of signaling pathways. At wound site, keratino